jbrowse-plugin-graphgenomeviewer 4.0.12 → 4.0.13

package/README.md

@@ -2,15 +2,30 @@
 
 Pangenome graphs in JBrowse 2.
 
-![KIV-2 as a graph track under a linear view, force-directed, with its bubbles marked](img/force_kiv2.png)
+## As a track of a linear view
 
-![KIV-2 walk rows: eight haplotypes tiled by the repeat unit](img/walk_rows_kiv2.png)
+A `GraphTrack` cuts the graph for the view's window and redraws it as you pan.
 
-![Tube maps, and a tube map track under a linear view](img/tube_map.png)
+![KIV-2 as a graph track under RefSeq genes, force-directed, with its bubbles marked](img/force_kiv2.png)
+
+![MICB's exons 2–4 as a tube map track, eight HPRC haplotypes, each reference node tied to its bp on the ruler](img/tube_map_micb_track.png)
+
+## As its own view
+
+**Add → Graph genome view** opens a whole GFA file. A graph track's **Launch →
+Graph genome view** opens the cut on screen, drawn as the track draws it; a
+session spec does the same with `loadedTrackId` and `loadedRegion`.
+
+![MICB's exons 2–4 as a tube map on its own axis, with the reference ruler under it](img/tube_map_micb.png)
+
+![KIV-2 walk rows: eight haplotypes, each copy coloured by its unit](img/walk_rows_kiv2.png)
+
+## Features
 
 - Eight layouts: force-directed (Bandage FMMM), variant map, ordered, anchored,
   sample rows, walk rows, and sequenceTubeMap's tube map on its own axis or the
   reference's
+- Genes from the session's annotation track, drawn on the graph
 - Bubbles from `gfatools bubble` or the graph itself, opened level by level
 - gbz-base haplotypes as walks: carriage as node thickness, one walk lifted out
 - GAF reads in the tube map, with their mismatches, from a gbz-base track
@@ -32,7 +47,6 @@ Needs JBrowse 5.0.0-beta.9 or later.
 
 - **File → Open track** opens an rGFA index (`.segs.bed.gz` from
   `build_rgfa_tabix.sh`) or a gbz-base database (`.gbz.db`) as a `GraphTrack`
-- **Add → Graph genome view** opens a whole GFA file
 - A hand-written track needs only the adapter:
 
 ```json
@@ -59,7 +73,9 @@ Needs JBrowse 5.0.0-beta.9 or later.
 - gbz-base swaps in `{ "type": "GbzBaseSyntenyAdapter", "uri": "….gbz.db" }`; an
   `hg38` or `hs1` track finds the graph's GRCh38 or CHM13 reference sample, and
   `assemblyNameToPanSN` covers other names
-- `"reads": "….gaf.gz"` on that adapter draws GAF reads in the tube map layouts
+- `"reads": "….gaf.gz"` on that adapter draws GAF reads in the tube map layouts,
+  fetched through its tabix index; [docs/layouts.md](docs/layouts.md#reads) has
+  the config and how to make one
 
 ## Docs
 

package/dist/chunks/GbzBaseSyntenyAdapter-Y5NBXK7P.js

@@ -0,0 +1,8 @@
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this.records.has(V(e,"forward"))}hasHandle(e){return this.records.has(e)}record(e){let t=this.records.get(e);if(!t)throw new Error(`Subgraph has no record for handle ${e}`);return t}sortedHandles(){return[...this.records.keys()].sort((e,t)=>e-t)}async addNode(e){if(this.signal?.throwIfAborted(),this.limit!==void 0&&this.nodeCount>=this.limit)throw new X(this.limit);let t=await this.db.getRecord(V(e,"forward")),n=await this.db.getRecord(V(e,"reverse"));if(!t||!n)throw new Error(`Node ${e} does not exist in the graph`);this.records.set(t.handle,t),this.records.set(n.handle,n)}async ensureNode(e){this.hasNode(e)||await this.addNode(e)}clearPaths(){this.paths=[],this.twinStarts.clear(),this.refId=void 0,this.refPath=void 0,this.refHandle=void 0,this.refInterval=void 0,this.refIndexCache=void 0,this.refPrefixCache=void 0}async pathPosition(e){let t=await this.db.findPath(e);if(!t)throw new Error(`Cannot find a path covering ${$(e,e.fragment)}`);if(!t.isIndexed)throw new Error(`Path 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prefetchReferenceRange(e,t,n){let[o,s]=await Promise.all([this.db.indexedPosition(e,t),this.db.indexedPosition(e,n)]);if(o&&s){let i=o.pos.node,a=s.pos.node;if(!await this.db.prefetchRecords(Math.min(i,a),Math.max(i,a)+1)){let c=await this.db.indexedPositionsBetween(e,t,n),l=ns(c.map(p=>p.pos.node));await Promise.all(l.map(([p,d])=>this.db.prefetchRecords(p,d+2)))}}return o}async aroundInterval(e,t,n){if(t===0)throw new Error("Interval length must be greater than 0");this.walkedBp=0;try{return await this.walkInterval(e,t,n)}catch(o){throw o instanceof X&&o.windowBp===void 0?new X(o.limit,{windowBp:t,walkedBp:this.walkedBp}):o}}get referenceWalkedBp(){return this.walkedBp}async walkInterval(e,t,n){let o={node:e.handle,offset:e.gbwtOffset},s=e.nodeOffset,i=t,a=new _e;for(;;){let f=A(o.node),c=ge(o.node);this.walkedBp=t-i,await this.ensureNode(f);let l=this.record(o.node);if(s>=l.sequenceLen)throw new Error(`Offset ${s} in node ${f} of length ${l.sequenceLen}`);a.push(s,f,He(c));let p=l.sequenceLen-s;if(i<=p){a.push(i===p?0:p-i-1,f,Ge(c));break}a.push(0,f,Ge(c));let d=l.gbwt().lf(o.offset);if(!d)throw new Error(`No successor for GBWT position (${o.node}, ${o.offset})`);o=d,s=0,i-=p}return this.walkedBp=t,this.insertContext(a,n)}async aroundNodes(e,t){let n=new _e;for(let o of e)await this.ensureNode(o),n.push(0,o,"left"),n.push(0,o,"right");return this.insertContext(n,t)}async insertContext(e,t){this.clearPaths();let n=new Set,o=new Set;for(let i of this.records.keys())o.add(A(i));let s=0;for(;e.size>0;){let[i,a,f]=e.pop(),c=`${a}:${f}`;if(n.has(c))continue;n.add(c),o.delete(a),this.hasNode(a)||(await this.addNode(a),s+=1);let l=Fn(f);if(!n.has(`${a}:${l}`)){let h=this.record(V(a,qn(f))),u=i+h.sequenceLen-1;u<=t&&e.push(u,a,l)}let p=this.record(V(a,$n(f))),d=i+1;if(d<=t)for(let h of p.successors()){let u=A(h),m=He(ge(h));n.has(`${u}:${m}`)||e.push(d,u,m)}}for(let i of o)this.records.delete(V(i,"forward")),this.records.delete(V(i,"reverse"));return{inserted:s,removed:o.size}}async betweenNodes(e,t){this.clearPaths();let n=[e,B(t)],o=new Set([A(e),A(t)]),s=0;for(;n.length>0;){let i=n.pop(),a=A(i);this.hasNode(a)||(await this.addNode(a),s+=1);for(let f of this.record(i).successors()){let c=A(f);o.has(c)||(n.push(f,B(f)),o.add(c))}}return s}async extractSnarls(e){let t=0;for(let[n,o]of await this.overlappingSnarls(e))t+=await this.betweenNodes(n,o);return t}async overlappingSnarls(e){let t=[];if(e!=="none"){let n=!1;for(let o of this.sortedHandles()){let s=this.record(o),i=s.next;i!==void 0&&(n=!0,this.hasHandle(i)?we(o,i)&&t.push([o,i]):e==="overlapping"&&this.isSnarlEntryInSubgraph(s)&&t.push([o,i]))}if(!n&&e==="overlapping"&&await this.db.hasChainLinks()){let o=await this.findCoveringSnarl();o&&t.push(o)}}return t}isSnarlEntryInSubgraph(e){let t=e.successors(),n=t.find(o=>this.hasHandle(o));return n===void 0?!1:t.length>1||this.record(B(n)).successors().length>1}recordReader(e){let t=new Map;return async n=>{let o=this.records.get(n);if(o)return o;let s=t.get(n);if(!s){if(s=await this.db.getRecord(n),e?.(),!s)throw new Error(`Node record ${n} is missing from the database`);t.set(n,s)}return s}}async findCoveringSnarl(){let e=this.recordReader(),t=async f=>{let c=f.successors(),l=c[0];return l===void 0?!1:c.length>1||(await e(B(l))).successors().length>1},n=async f=>{let c=await e(B(f));return c.next!==void 0?await t(c)?{kind:"snarl-exit",snarl:[B(f),c.next]}:{kind:"chain"}:(await e(f)).next!==void 0?{kind:"chain"}:{kind:"regular"}},o=new Set,s=this.sortedHandles().flatMap(f=>this.record(f).successors()),i,a=!1;for(;!a&&s.length>0;){let f=s.shift(),c=A(f);if(!this.hasHandle(f)&&!o.has(c)){o.add(c);let l=await n(f);if(l.kind==="snarl-exit")i=l.snarl,a=!0;else if(l.kind==="chain")a=!0;else for(let p of["forward","reverse"])s.push(...(await e(V(c,p))).successors())}}return i}extractPaths(e,t){if(this.clearPaths(),t==="none")return;let n=e?.position;this.refPath=e?.name,this.refHandle=e?.handle;let o=this.sortedHandles(),s=o.length,i=new Map;o.forEach((y,v)=>i.set(y,v));let a=new Int32Array(s+1),f=new Int32Array(s),c=[];for(let y=0;y<s;y++){let v=this.record(o[y]),I=v.gbwt().decompressArrays();f[y]=v.sequenceLen,c.push(I),a[y+1]=a[y]+I.nodes.length}let l=a[s],p=new Int32Array(l),d=new Int32Array(l),h=new Uint8Array(l);for(let y=0;y<s;y++){let v=c[y];p.set(v.nodes,a[y]),d.set(v.offsets,a[y])}c.length=0;for(let y=0;y<l;y++){let v=i.get(p[y]);v===void 0?p[y]=-1:(p[y]=v,h[a[v]+d[y]]=1)}let u=n===void 0?void 0:i.get(n.handle),m=n?.gbwtOffset,w,x=(y,v,I)=>{let R=[],C=0,P=0,E=-1,M=y,L=v;for(;;){M===u&&L===m&&(E=C),I&&(I.push(o[M]),R.push(L)),C+=1,P+=f[M];let N=a[M]+L,F=p[N];if(F<0)break;L=d[N],M=F}return{offsets:R,len:P,refAt:E,last:M}},S=(y,v,I,R)=>{R>=0&&(this.refId=this.paths.length,w=R),this.paths.push({path:y,offsets:v,len:I,weight:void 0,identity:void 0})},g=new Int32Array(s),b=u!==void 0&&O(o[u]);for(let y=0;y<s;y++){let v=o[y];if(!O(v)){let I=a[y],R=a[y+1]-I;for(let C=0;C<R;C++)if(h[I+C]===0){let P=[],{offsets:E,len:M,refAt:L,last:N}=x(y,C,P),F=o[N];if(L>=0||Be(v,F)){if(S(P,E,M,L),!O(F)){let q=i.get(B(F));g[q]=g[q]+1}}else this.twinStarts.add(fe({node:v,offset:C}))}}}for(let y=0;y<s;y++){let v=o[y];if(O(v)){let I=a[y],R=a[y+1]-I,C=0;for(let E=0;E<R;E++)h[I+E]===0&&(C+=1);let P=!b&&C===g[y];for(let E=0;E<R;E++)if(h[I+E]===0){let M=P?void 0:x(y,E,void 0);if(M&&(M.refAt>=0||Be(v,o[M.last]))){let L=[],{offsets:N,len:F,refAt:q}=x(y,E,L);S(L,N,F,q)}else this.twinStarts.add(fe({node:v,offset:E}))}}}if(n){if(w===void 0||this.refId===void 0)throw this.clearPaths(),new Error("Could not find the reference path");let y=this.paths[this.refId],v=n.nodeOffset;for(let R of y.path.slice(0,w))v+=this.record(R).sequenceLen;let I=n.seqOffset-v;this.refInterval=[I,I+y.len],y.identity={pathHandle:e.handle,name:e.name,orientation:"forward",hapStart:I,hapEnd:I+y.len}}if(t==="distinct")this.distinctPaths();else if(t==="reference-only"){if(this.refId===void 0)throw new Error("Reference path is required for reference-only output");this.paths=[this.paths[this.refId]],this.refId=0}}distinctPaths(){let e=this.refId===void 0?void 0:this.paths[this.refId].path;this.paths.sort((o,s)=>Vt(o.path,s.path)||o.len-s.len);let t=[],n;for(let o of this.paths){let s=t[t.length-1];s&&Vt(s.path,o.path)===0?s.weight=(s.weight??0)+1:(e&&Vt(o.path,e)===0&&(n=t.length),t.push({...o,weight:1}))}this.paths=t,this.refId=n}keepHaplotypes(e){let t=this.refId===void 0?void 0:this.paths[this.refId],n=this.paths.filter((s,i)=>i===this.refId||s.identity!==void 0&&e(s.identity.name)),o=new Set;for(let s of n)for(let i of s.path)o.add(A(i));for(let s of[...this.records.keys()])o.has(A(s))||this.records.delete(s);this.paths=n,this.refId=t===void 0?void 0:n.indexOf(t)}async walkHaplotypesFromAnchor(e,t,n,o,s){let i=e.position.seqOffset,a=i+t,f=Math.floor(i/n)*n,c=Math.min(n,ts),l=4*(n+t)+c,p={spacing:n,anchorOffset:f,anchorNodeOffset:-1,anchorHandle:-1,referenceSteps:0,rows:0,walks:[],graphFetches:0,scans:[],scanRows:0,fallback:void 0,ms:{reference:0,rows:0,walks:0,scan:0,sampled:0}};this.stats.anchorWalk=p;let d=performance.now(),h=()=>{let k=performance.now(),U=k-d;return d=k,U};this.clearPaths(),this.records.clear();let u=this.recordReader(()=>{p.graphFetches+=1}),m=await this.db.haplotypeAnchor(e.handle,f);if(m===void 0)throw new Error(`The haplotype index names no anchor for ${$(e.name,e.name.fragment)} at offset ${f}; it was not built with anchors at ${n} bp for this graph`);p.anchorNodeOffset=m.pathOffset;let w=await this.prefetchReferenceRange(e.handle,m.pathOffset,a+c);if(!w)throw new Error(`Path ${$(e.name,e.name.fragment)} has not been indexed for random access`);let x=await this.walkReference(u,w,m,i,a,a+c),{anchor:S,refOffsetOf:g,refHandles:b,windowSteps:y}=x;p.anchorHandle=S.pos.node,p.referenceSteps=x.steps,this.walkedBp=t;let v=[],I=[],R=0;for(let k of y)await this.ensureNode(A(k.pos.node)),v.push(k.pos.node),I.push(k.pos.offset),R+=this.record(k.pos.node).sequenceLen;let C=y[0];if(C===void 0)throw new Error("The reference walk has no node in the window");this.refPath=e.name,this.refHandle=e.handle,this.refInterval=[C.refOffset,C.refOffset+R],this.refId=0,this.paths.push({path:v,offsets:I,len:R,weight:void 0,identity:{pathHandle:e.handle,name:e.name,orientation:"forward",hapStart:C.refOffset,hapEnd:C.refOffset+R}}),p.ms.reference=h();let P=await this.db.haplotypeSamplesAtNode(S.pos.node);p.rows=P.length,p.ms.rows=h();let E=P.find(k=>k.offset===S.pos.offset&&k.pathHandle===e.handle&&k.pathOffset===S.offset);if(E===void 0)throw new Error(`The haplotype index has no anchor row for ${$(e.name,e.name.fragment)} at offset ${S.offset} (node ${A(S.pos.node)}); it was not built with anchors at ${n} bp for this graph`);let M=await this.db.pathsByHandle(),L=k=>{let U=M.get(k);if(!U)throw new Error(`Path ${k} is missing from the database`);return U.name},N=new Set([e.handle]),F=new Map;for(let k of P)if(k!==E&&o(L(k.pathHandle))){let U=F.get(k.pathHandle);U?U.push(k):F.set(k.pathHandle,[k])}let q;for(let[k,U]of F)if(q===void 0){let de=ie=>Math.abs(ie.offset-E.offset);U.sort((ie,Io)=>de(ie)-de(Io));let he;for(let ie of U)N.has(k)||(he=await this.walkAndKeep(u,ie,"anchor",L(k),g,a,l,s,N,p));N.has(k)||(q=he)}p.ms.walks=h();let Ee=q===void 0?await this.samplesOfUnwalkedContigs(v,g,b,o,N,L,p):new Map;if(p.ms.scan=h(),Ee.size>0){await this.mapReferenceBefore(u,e.handle,Math.max(0,m.pathOffset-2*n),m.pathOffset,g,b);for(let[k,U]of Ee)if(q===void 0){let de=L(k),he;for(let ie of U)he??=await this.entryBefore(u,ie,g,b,this.refInterval[0],l);q=he===void 0?`no sample of ${$(de,de.fragment)} on the window's nodes runs with the reference`:await this.walkAndKeep(u,he,"sample",de,g,a,l,s,N,p)}p.ms.sampled=h()}return p.fallback=q,q}async walkAndKeep(e,t,n,o,s,i,a,f,c,l){let p=await this.walkFromRow(e,t,o,s,this.refInterval[0],i,a,f);l.walks.push({pathHandle:t.pathHandle,from:n,steps:p.steps,pieces:p.infos.length,end:p.end});let d;return p.end==="bound"||p.infos.length===0?d=`${$(o,t.pathOffset)} walked ${p.steps} steps from its ${n} without writing a walk through the window (${p.end})`:(c.add(t.pathHandle),this.paths.push(...p.infos)),d}async mapReferenceBefore(e,t,n,o,s,i){let a=await this.prefetchReferenceRange(t,n,o),f=a?.pos,c=a?.pathOffset??o;for(;f!==void 0&&f.node!==0&&c<o;){this.signal?.throwIfAborted();let l=await e(f.node),p=A(f.node);s.has(p)||(s.set(p,c),i.add(f.node)),c+=l.sequenceLen,f=l.gbwt().lf(f.offset)}}async runsWithReference(e,t,n,o,s){let i={node:t.node,offset:t.offset},a=0,f;for(;f===void 0;)if(this.signal?.throwIfAborted(),i===void 0||i.node===0||a>s)f=!1;else if(n.has(A(i.node)))f=o.has(i.node);else{let c=await e(i.node);a+=c.sequenceLen,i=c.gbwt().lf(i.offset)}return f}async entryBefore(e,t,n,o,s,i){let a=(await e(t.node)).sequenceLen,f=async(h,u)=>{let m=(await e(h.node)).sequenceLen;return{node:h.node,offset:h.offset,pathHandle:t.pathHandle,orientation:t.orientation,pathOffset:t.orientation==="forward"?t.pathOffset-u:t.pathOffset+a+u-m}},c={node:t.node,offset:t.offset},l=0,p,d=!await this.runsWithReference(e,t,n,o,i);for(;!d;){this.signal?.throwIfAborted();let h=n.get(A(c.node));if(h!==void 0&&h<s)p=await f(c,l),d=!0;else if(l>i)p={...t},d=!0;else{let m=(await e(B(c.node))).gbwt().predecessorAt(c.offset);if(m===void 0)p=await f(c,l),d=!0;else{let w=await e(m),x=w.gbwt().offsetTo(c);if(x===void 0)throw new Error(`No offset in ${m} leads to ${c.node}:${c.offset}`);c={node:m,offset:x},l+=w.sequenceLen}}}return p}async walkReference(e,t,n,o,s,i){let a=new Map,f=new Set,c=[],l,p=t.pos,d=t.pathOffset,h=0;for(;p!==void 0&&p.node!==0&&d<i;){this.signal?.throwIfAborted();let u=await e(p.node),m=d+u.sequenceLen;if(l===void 0&&d===n.pathOffset){if(p.node!==n.node)throw new Error(`The reference walk reaches node ${A(p.node)} at offset ${d} where the haplotype index names node ${A(n.node)} as the anchor`);l={pos:p,offset:d}}if(l!==void 0){h+=1;let w=A(p.node);a.has(w)||(a.set(w,d),f.add(p.node)),d<s&&m>o&&c.push({pos:p,refOffset:d})}d=m,p=u.gbwt().lf(p.offset)}if(l===void 0)throw new Error(`The reference walk from offset ${t.pathOffset} never starts a node at the anchor offset ${n.pathOffset}`);return{anchor:l,refOffsetOf:a,refHandles:f,windowSteps:c,steps:h}}async walkFromRow(e,t,n,o,s,i,a,f){let c=(await e(t.node)).sequenceLen,l=t.orientation==="forward"?t.pathOffset:t.pathOffset+c,p=[],d=[],h=[],u=0,m=0,w=0,x,S,g={node:t.node,offset:t.offset};for(;S===void 0;)if(this.signal?.throwIfAborted(),g===void 0||g.node===0)S=x===void 0?"before the window":"ended in the window";else if(m>a)S="bound";else{let y=o.get(A(g.node)),v=x!==void 0;if(y!==void 0&&y>=i)S=v?"through the window":"past the window";else{!v&&y!==void 0&&y>=s&&(x=m);let I=await e(g.node);if(x!==void 0){let R={pos:g,at:m,len:I.sequenceLen};y===void 0?(h.push(R),u+=R.len):(u>f&&y<s?(p.push(d),d=[]):d.push(...h),h=[],u=0,d.push(R))}w+=1,m+=I.sequenceLen,g=I.gbwt().lf(g.offset)}}p.push(d);let b=[];for(let y of p){let v=y[0],I=y[y.length-1];if(v!==void 0&&I!==void 0){let R=[],C=[],P=0;for(let L of y)await this.ensureNode(A(L.pos.node)),R.push(L.pos.node),C.push(L.pos.offset),P+=L.len;let E=v.at,M=I.at+I.len;b.push({path:R,offsets:C,len:P,weight:void 0,identity:t.orientation==="forward"?{pathHandle:t.pathHandle,name:n,orientation:"forward",hapStart:l+E,hapEnd:l+M}:{pathHandle:t.pathHandle,name:n,orientation:"reverse",hapStart:l-M,hapEnd:l-E}})}}return{steps:w,end:S,infos:b}}async samplesOfUnwalkedContigs(e,t,n,o,s,i,a){let f=dr([...e].sort((l,p)=>l-p));a.scans=f;let c=new Map;for(let[l,p]of f){let d=await this.db.haplotypeSamplesInRange(l,p);a.scanRows+=d.length;for(let h of d){let u=t.has(A(h.node));if(!s.has(h.pathHandle)&&(!u||n.has(h.node))&&o(i(h.pathHandle))){let m=c.get(h.pathHandle)??[];u?m.unshift(h):m.push(h),c.set(h.pathHandle,m)}}}return c}async identifyPaths(){if(!this.db.hasHaplotypeIndex)throw new Error("The database has no HaplotypeSamples table; run gbz-haplotype-index on it");let e=await this.db.haplotypeSampleInterval()??4096,t=dr(this.sortedHandles());if(t.length===0)return;let n=new Map;for(let[u,m]of t)for(let w of await this.db.haplotypeSamplesInRange(u,m))n.set(fe(w),w);let o=u=>{let m=0,w=t.length-1;for(;m<w;){let S=m+w+1>>1;t[S][0]<=u?m=S:w=S-1}let x=t[m];return x[0]<=u&&u<=x[1]},s=new Map;this.paths.forEach((u,m)=>{u.path.length>0&&m!==this.refId&&s.set(fe(Ke(u,0)),m)});let i=this.stats.identification;i.interval=e,i.scans=t,i.windowSamples=n.size,this.paths.forEach((u,m)=>{m!==this.refId&&i.fragmentLengths.push(u.len)});let a=this.recordReader(()=>{this.stats.identificationFetches+=1,i.graphFetches+=1}),f=u=>(i.graphLookups+=1,a(u)),c=async(u,m)=>{if(o(u.node))return n.get(fe(u));this.stats.identificationFetches+=1,i.companionSeeks+=1,m.seeks+=1;let w=await this.db.haplotypeSampleAt(u.node,u.offset);return w||(i.companionMisses+=1),w},l=new Map,p=async u=>{let m=l.get(u);if(!m){let w=await this.db.getPath(u);if(!w)throw new Error(`Path ${u} is missing from the database`);m=w.name,l.set(u,m)}return m},d=(u,m,w)=>u.orientation==="forward"?{pathHandle:u.pathHandle,orientation:"forward",base:u.pathOffset-m}:{pathHandle:u.pathHandle,orientation:"reverse",base:u.pathOffset+m+w},h=(u,m)=>u.orientation==="forward"?{pathHandle:u.pathHandle,orientation:"forward",base:u.hapStart-m}:{pathHandle:u.pathHandle,orientation:"reverse",base:u.hapEnd+m};for(let u=0;u<this.paths.length;u++){let m=this.paths[u];if(u===this.refId||m.identity)continue;let w=[],x=new Set,S={fragments:0,steps:0,seeks:0,reentries:0,twinLandings:0,end:"endmarker",pathHandle:void 0};i.chains.push(S);let g,b=0,y=u,v;for(;g===void 0;){if(this.signal?.throwIfAborted(),y!==void 0){if(x.has(y)){S.end="cycle";break}x.add(y);let E=this.paths[y];w.push({index:y,startBp:b}),S.fragments+=1;let M=b;for(let N=0;N<E.path.length;N++){let F=Ke(E,N),q=n.get(fe(F)),Ee=this.record(F.node).sequenceLen;if(q){g=d(q,M,Ee);break}M+=Ee}if(b+=E.len,g){S.end="in-fragment sample";break}let L=Ke(E,E.path.length-1);v=this.record(L.node).gbwt().lf(L.offset),y=void 0}if(v===void 0||v.node===0){S.end="endmarker";break}let I=fe(v),R=s.get(I);if(R!==void 0){let E=this.paths[R].identity;if(E){g=h(E,b),S.end="identified sibling";break}y=R;continue}this.records.has(v.node)&&(S.reentries+=1),this.twinStarts.has(I)&&(S.twinLandings+=1);let C=await c(v,S),P=await f(v.node);if(C){g=d(C,b,P.sequenceLen),S.end="out-of-window sample";break}if(this.stats.identificationSteps+=1,S.steps+=1,b-w[w.length-1].startBp>4*e+4*P.sequenceLen){S.end="bound";break}b+=P.sequenceLen,v=P.gbwt().lf(v.offset)}if(g){S.pathHandle=g.pathHandle;let I=await p(g.pathHandle);for(let{index:R,startBp:C}of w){let P=this.paths[R];P.identity=g.orientation==="forward"?{pathHandle:g.pathHandle,name:I,orientation:"forward",hapStart:g.base+C,hapEnd:g.base+C+P.len}:{pathHandle:g.pathHandle,name:I,orientation:"reverse",hapStart:g.base-C-P.len,hapEnd:g.base-C}}}}}refIndex(e){if(this.refIndexCache===void 0){let t=new Map;e.forEach((n,o)=>{let s=t.get(n);s?s.push(o):t.set(n,[o])}),this.refIndexCache=t}return this.refIndexCache}refPrefix(e){if(this.refPrefixCache===void 0){let t=[0];e.forEach((n,o)=>{t.push(t[o]+this.record(n).sequenceLen)}),this.refPrefixCache=t}return this.refPrefixCache}orderedMatches(e,t){let n=this.refIndex(t),o=new Int32Array(e.length),s=new Int32Array(e.length),i=0,a=-1;for(let f=0;f<e.length;f++){let c=n.get(e[f]);if(c){let l=Vo(c,a);if(l===void 0)return;o[i]=f,s[i]=l,i+=1,a=l}}return{pathAt:o,refAt:s,count:i}}pathLen(e){let t=0;for(let n of e)t+=this.record(n).sequenceLen;return t}prefixMatches(e,t){let n=0,o=0,s=0,i=0,a=0;for(;o<e.length&&s<t.length;){let f=this.record(e[o]).sequence,c=this.record(t[s]).sequence;for(;i<f.length&&a<c.length;){if(f[i]!==c[a])return n;i+=1,a+=1,n+=1}i===f.length&&(o+=1,i=0),a===c.length&&(s+=1,a=0)}return n}suffixMatches(e,t){let n=0,o=0,s=0,i=0,a=0;for(;o<e.length&&s<t.length;){let f=this.record(e[e.length-o-1]).sequence,c=this.record(t[t.length-s-1]).sequence;for(;i<f.length&&a<c.length;){if(f[f.length-i-1]!==c[c.length-a-1])return n;i+=1,a+=1,n+=1}i===f.length&&(o+=1,i=0),a===c.length&&(s+=1,a=0)}return n}align(e,t,n){let o=this.pathLen(e),s=this.pathLen(t),i=this.prefixMatches(e,t),a=this.suffixMatches(e,t);i+a>o&&(a=o-i),i+a>s&&(a=s-i),z(n,"M",i),hr(n,o-i-a,s-i-a),z(n,"M",a)}sharedWeight(e,t){let n=this.refIndex(t),o=0;for(let s of e)n.has(s)&&(o+=this.record(s).sequenceLen);return o}editsAgainst(e,t){let n=this.orderedMatches(e,t);n?this.stats.orderedAlignments+=1:this.stats.lcsAlignments+=1;let o=n??Yo(Zn(e,t,p=>this.record(p).sequenceLen)[0]),s=[],i=this.refPrefix(t),a=(p,d,h,u)=>{p===d?z(s,"D",i[u]-i[h]):h===u?z(s,"I",this.pathLen(e.slice(p,d))):this.align(e.slice(p,d),t.slice(h,u),s)},f=0,c=0,l=0;for(let p=0;p<o.count;p++){let d=o.pathAt[p],h=o.refAt[p];(c!==d||l!==h)&&a(c,d,l,h);let u=this.record(e[d]).sequenceLen;z(s,"M",u),f+=u,c=d+1,l=h+1}return a(c,e.length,l,t.length),{edits:s,matched:f}}alignment(e){let t=this.paths[e];if(this.refId===void 0||e===this.refId||!t)return;let n=this.paths[this.refId].path,o;if(Hn(n))o={edits:this.editsAgainst(t.path,n).edits,flipped:!1};else{let s=t.path.map(f=>B(f)).reverse(),i=this.sharedWeight(t.path,n);if(this.sharedWeight(s,n)===0)o={edits:this.editsAgainst(t.path,n).edits,flipped:!1};else if(i===0)o={edits:this.editsAgainst(s,n).edits,flipped:!0};else{let f=this.editsAgainst(t.path,n),c=this.editsAgainst(s,n);o=c.matched>f.matched?{edits:c.edits,flipped:!0}:{edits:f.edits,flipped:!1}}}return o}alignToRef(e){return this.alignment(e)?.edits.map(([t,n])=>`${n}${t}`).join("")}alignments(){let e=this.referenceInterval;if(this.refId===void 0||!e)throw new Error("Alignments need a reference path");let t=this.paths[this.refId].path,n=this.refPrefix(t)[t.length],o=[];return this.paths.forEach((s,i)=>{if(i===this.refId)return;let{edits:a,flipped:f}=this.alignment(i),c=0,l=0;for(;c<a.length&&a[c][0]==="D";)l+=a[c][1],c+=1;let p=a.length,d=0;for(;p>c&&a[p-1][0]==="D";)d+=a[p-1][1],p-=1;let h=s.identity,u=h?h.orientation==="forward"!==f:!f;o.push({strand:u?"+":"-",refStart:e.start+l,refEnd:e.start+n-d,edits:a.slice(c,p),weight:s.weight,path:s.path,start:Ke(s,0),identity:h===void 0?void 0:{pathHandle:h.pathHandle,name:h.name,hapStart:h.name.fragment+h.hapStart,hapEnd:h.name.fragment+h.hapEnd,walkForward:h.orientation==="forward"}})}),Zo(o).map(s=>{let{edits:i,identity:a,...f}=s,c={...f,cigar:os(i)};return a?{...c,resolved:!0,name:a.name,label:$({...a.name,fragment:a.hapStart},a.hapEnd),pathHandle:a.pathHandle,hapStart:a.hapStart,hapEnd:a.hapEnd}:{...c,resolved:!1}})}pairAlignments(e){let{target:t,query:n,...o}=e,s=this.paths.flatMap(l=>{let{identity:p}=l;return p?[{name:p.name,start:p.name.fragment+p.hapStart,steps:Ze(l,p)}]:[]}),i=l=>p=>p.sample===l.sample&&p.haplotype===l.haplotype,a=i(t),f=n?i(n):l=>!a(l),c=l=>this.record(V(l,"forward")).sequence;return s.filter(l=>a(l.name)).flatMap(l=>s.filter(p=>f(p.name)).flatMap(p=>lr(p.steps,l.steps,c,o).map(d=>({query:p.name,queryStart:p.start+d.queryStart,queryEnd:p.start+d.queryEnd,strand:d.strand,target:l.name,targetStart:l.start+d.targetStart,targetEnd:l.start+d.targetEnd,cigar:pr(d.edits),matches:d.edits.reduce((h,[u,m])=>h+(u==="="?m:0),0),columns:d.edits.reduce((h,[,u])=>h+u,0),sharedBases:d.sharedBases}))))}canonicalEdges(e){let t=[];for(let n of["forward","reverse"]){let o=V(e,n);for(let s of this.record(o).successors())this.hasHandle(s)&&we(o,s)&&t.push([n==="reverse"?1:0,A(s),O(s)?1:0])}return t.sort((n,o)=>n[0]-o[0]||n[1]-o[1]||n[2]-o[2]),t.filter((n,o)=>o===0||n[0]!==t[o-1][0]||n[1]!==t[o-1][1]||n[2]!==t[o-1][2])}async stableName(){let e=new TextEncoder,t=[];for(let n of this.sortedHandles())if(!O(n)){let o=A(n),s=`S	${o}	${this.record(n).sequence}
+`;for(let[i,a,f]of this.canonicalEdges(o))s+=`L	${o}	${i?"-":"+"}	${a}	${f?"-":"+"}
+`;t.push(e.encode(s))}return Kn(t)}async toGFA(e={}){let t=e.cigar??!1,n=[this.refPath?`H	VN:Z:1.1	RS:Z:${this.refPath.sample}`:"H	VN:Z:1.1",...Vn(Yn(await this.stableName(),await this.db.graphName()))],o=this.sortedHandles();for(let c of o)O(c)||n.push(`S	${A(c)}	${this.record(c).sequence}`);let s=c=>O(c)?"-":"+";for(let c of o)for(let l of this.record(c).successors())this.hasHandle(l)&&we(c,l)&&n.push(`L	${A(c)}	${s(c)}	${A(l)}	${s(l)}	0M`);let i=(c,l,p,d,h)=>{let u=Ze(c,l).map(x=>`${O(x)?"<":">"}${A(x)}`).join(""),m=c.weight===void 0?"":`	WT:i:${c.weight}`,w=h===void 0?"":`	CG:Z:${h}`;return`W	${p.sample}	${p.haplotype}	${p.contig}	${p.fragment}	${d}	${u}${m}${w}`},a=this.refPath?.contig??"unknown";this.refId!==void 0&&this.refPath&&this.refInterval&&n.push(i(this.paths[this.refId],void 0,{...this.refPath,fragment:this.refPath.fragment+this.refInterval[0]},this.refPath.fragment+this.refInterval[1],void 0));let f=1;return this.paths.forEach((c,l)=>{if(l!==this.refId){let p=e.names==="resolved"?c.identity:void 0,d=t?this.alignToRef(l):void 0;n.push(p?i(c,p,{...p.name,fragment:p.name.fragment+p.hapStart},p.name.fragment+p.hapEnd,d):i(c,void 0,{sample:"unknown",contig:a,haplotype:f,fragment:0},c.len,d)),f+=1}}),`${n.join(`
+`)}
+`}outputPaths(e){let t=e.cigar??!1,n=[],o=this.refPath?.contig??"unknown";if(this.refId!==void 0&&this.refPath&&this.refInterval){let i={...this.refPath,fragment:this.refPath.fragment+this.refInterval[0]};n.push({info:this.paths[this.refId],identity:void 0,name:$(i,this.refPath.fragment+this.refInterval[1]),cigar:void 0})}let s=1;return this.paths.forEach((i,a)=>{if(a===this.refId)return;let f=e.names==="resolved"?i.identity:void 0;n.push({info:i,identity:f,name:f?$({...f.name,fragment:f.name.fragment+f.hapStart},f.name.fragment+f.hapEnd):$({sample:"unknown",contig:o,haplotype:s,fragment:0},i.len),cigar:t?this.alignToRef(a):void 0}),s+=1}),n}*outputEdges(){for(let e of this.sortedHandles())for(let t of this.record(e).successors())this.hasHandle(t)&&we(e,t)&&(yield[e,t])}toSubgraphJson(e={}){let t=this.sortedHandles().filter(s=>!O(s)).map(s=>({id:String(A(s)),sequence:this.record(s).sequence})),n=[];for(let[s,i]of this.outputEdges())n.push({from:String(A(s)),from_is_reverse:O(s),to:String(A(i)),to_is_reverse:O(i)});let o=this.outputPaths(e).map(s=>rs(s.info,s.identity,s.name,s.cigar));return{nodes:t,edges:n,paths:o}}toCompactSubgraph(e={}){let t=this.sortedHandles().filter(i=>!O(i)),n=new Int32Array(t.length),o=[];t.forEach((i,a)=>{n[a]=A(i),o.push(this.record(i).sequence)});let s=[];for(let[i,a]of this.outputEdges())s.push(i,a);return{nodeIds:n,nodeSequences:o,edges:Int32Array.from(s),paths:this.outputPaths(e).map(i=>({name:i.name,weight:i.info.weight,cigar:i.cigar,steps:Int32Array.from(Ze(i.info,i.identity))}))}}};function Ze(r,e){return e?.orientation==="reverse"?r.path.map(t=>B(t)).reverse():r.path}function rs(r,e,t,n){return{name:t,...r.weight===void 0?{}:{weight:r.weight},...n===void 0?{}:{cigar:n},path:Ze(r,e).map(o=>({id:String(A(o)),is_reverse:O(o)}))}}function Vt(r,e){let t=Math.min(r.length,e.length);for(let n=0;n<t;n++){let o=r[n],s=e[n];if(o!==s)return o<s?-1:1}return r.length-e.length}function z(r,e,t){if(t===0)return;let n=r[r.length-1];n?.[0]===e?n[1]+=t:r.push([e,t])}function Xe(r){return r===0?0:6+(r-1)}function hr(r,e,t){if(e===0)z(r,"D",t);else if(t===0)z(r,"I",e);else{let n=Math.min(e,t),o=4*n+Xe(e-n)+Xe(t-n),s=Xe(e)+Xe(t);o<=s?(z(r,"M",n),z(r,"I",e-n),z(r,"D",t-n)):(z(r,"I",e),z(r,"D",t))}}function os(r){return r.map(([e,t])=>`${t}${e}`).join("")}async function Je(r,e,t,n,o={}){let s=new Me(r,o);try{let i=await s.pathPosition(Pe(e,t));await s.prefetchReferenceWalk(i,n-t),await s.aroundInterval(i.position,n-t,o.context??100),await s.extractSnarls(o.snarls??"none"),s.extractPaths(i,o.haplotypes??"all")}catch(i){throw i instanceof X&&i.windowBp===void 0?new X(i.limit,{windowBp:n-t,walkedBp:s.referenceWalkedBp??0}):i}return s}async function ur(r,e,t,n,o){if(!r.hasHaplotypeIndex)throw new Error("keep needs the haplotype index: this database cannot name its walks");let s=await r.haplotypeAnchorSpacing(),i,a;if(s!==void 0&&(o.haplotypes??"all")==="all"){let f=new Me(r,o);try{let c=await f.pathPosition(Pe(e,t));a=await f.walkHaplotypesFromAnchor(c,n-t,s,o.keep,o.context??100)}catch(c){throw c instanceof X&&c.windowBp===void 0?new X(c.limit,{windowBp:n-t,walkedBp:f.referenceWalkedBp??0}):c}if(a===void 0)i=f;else{a=`${a}; identified from the per-path samples instead`;let c=await Je(r,e,t,n,o);await c.identifyPaths(),c.keepHaplotypes(o.keep),c.stats.anchorWalk=f.stats.anchorWalk,c.stats.anchorWalk&&(c.stats.anchorWalk.fallback=a),i=c}}else i=await Je(r,e,t,n,o),await i.identifyPaths(),i.keepHaplotypes(o.keep);return i}function Z(r,e){let t=0;for(let o=0;o<8;o++){let s=r[e+o];if(s===void 0)throw new Error("SQLite varint runs past the end of the buffer");if(t=t*128+(s&127),(s&128)===0)return[t,e+o+1]}let n=r[e+8];if(n===void 0)throw new Error("SQLite varint runs past the end of the buffer");if(t=t*256+n,!Number.isSafeInteger(t))throw new Error("SQLite varint exceeds the safe integer 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u=d;u<=h;u++)f.push(u===l.cellCount?l.rightChild:oe(c,ne(c,l,u)))}),f.length>cs)return!1;this.pager.prefetch(f),s=f}return!0}async tableRowid(e,t){let n=e;for(;;){let{page:o,header:s}=await this.pageAt(n);if(s.type===tt){let f=0,c=s.cellCount;for(;f<c;){let l=f+c>>1,p=ne(o,s,l),[d,h]=Z(o,p),[u,m]=Z(o,h);if(u===t)return et(await this.payload(o,m,d,!1));u<t?f=l+1:c=l}return}if(s.type!==nt)throw new Error("SQLite table b-tree contains an index page");let i=0,a=s.cellCount;for(;i<a;){let f=i+a>>1,c=ne(o,s,f),[l]=Z(o,c+4);l<t?i=f+1:a=f}n=i===s.cellCount?s.rightChild:oe(o,ne(o,s,i))}}async*tableScan(e){let{page:t,header:n}=await this.pageAt(e);if(n.type===tt)for(let o=0;o<n.cellCount;o++){let s=ne(t,n,o),[i,a]=Z(t,s),[f,c]=Z(t,a);yield{rowid:f,values:et(await this.payload(t,c,i,!1))}}else{let o=[];for(let s=0;s<n.cellCount;s++)o.push(oe(t,ne(t,n,s)));o.push(n.rightChild),this.pager.prefetch(o);for(let s of o)yield*this.tableScan(s)}}decodedCells(e,t){let n=this.decodedIndexPages.get(e);if(n)this.decodedIndexPages.delete(e);else if(n=new Array(t.cellCount),this.decodedIndexPages.size>=fs){let o=this.decodedIndexPages.keys().next().value;o!==void 0&&this.decodedIndexPages.delete(o)}return this.decodedIndexPages.set(e,n),n}async indexCell(e,t,n,o){let s=this.decodedCells(e,n),i=s[o];if(!i){let a=ne(t,n,o),f=n.type===ke,[c,l]=Z(t,f?a+4:a);i={values:et(await this.payload(t,l,c,!0)),leftChild:f?oe(t,a):0},s[o]=i}return i}async*indexScanFrom(e,t){let{page:n,header:o}=await this.pageAt(e),s=0,i=o.cellCount;for(;s<i;){let a=s+i>>1,f=await this.indexCell(e,n,o,a);mr(f.values,t)<0?s=a+1:i=a}for(let a=s;a<o.cellCount;a++){let f=await this.indexCell(e,n,o,a);o.type===ke&&(yield*this.indexScanFrom(f.leftChild,t)),yield f.values}o.type===ke&&(yield*this.indexScanFrom(o.rightChild,t))}async indexSeekLE(e,t){let n,o=e;for(;;){let{page:s,header:i}=await this.pageAt(o),a=0,f=i.cellCount,c=0;for(;a<f;){let l=a+f>>1,p=await this.indexCell(o,s,i,l);mr(p.values,t)<=0?(n=p.values,a=l+1):(c=p.leftChild,f=l)}if(i.type===gr)return n;o=a===i.cellCount?i.rightChild:c}}};function mr(r,e){for(let t=0;t<e.length;t++){let n=r[t],o=e[t];if(typeof n!="number"||o===void 0)throw new Error("SQLite index key is not numeric");if(n!==o)return n<o?-1:1}return 0}var ot=class{blocks=new Map;blockSize;maxBlocks;bytesFetched=0;fetches=0;source;pageSize;fileSize;constructor(e,t,n,o={}){this.source=e,this.pageSize=t,this.fileSize=n;let s=o.blockSize??65536;this.blockSize=Math.max(t,Math.ceil(s/t)*t),this.maxBlocks=o.maxBlocks??256}async read(e,t){let n=0;for(;;)try{let o=await this.source.read(e,t);return this.bytesFetched+=o.length,o}catch(o){if(n+=1,n>=3)throw o;await new Promise(s=>setTimeout(s,200*n))}}seed(e,t){t.length===Math.min(this.blockSize,this.fileSize-e*this.blockSize)&&this.blocks.set(e,Promise.resolve(t))}block(e){let t=this.blocks.get(e);if(t)return this.blocks.delete(e),this.blocks.set(e,t),t;let 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outside the file`);let n=await this.block(Math.floor(t/this.blockSize)),o=t%this.blockSize;return n.subarray(o,o+this.pageSize)}};var Le=class r{pager;btree;objects;constructor(e,t,n){this.pager=e,this.btree=t,this.objects=n}static async open(e,t={}){let{size:n}=await e.stat(),o=await e.read(Math.min(t.blockSize??65536,n),0),s=o.subarray(0,100);if(new TextDecoder().decode(s.subarray(0,15))!=="SQLite format 3")throw new Error("Not a SQLite database");let a=new DataView(s.buffer,s.byteOffset,s.byteLength),f=a.getUint16(16),c=f===1?65536:f,l=s[20]??0,p=a.getUint32(56);if(p!==1)throw new Error(`SQLite text encoding ${p} is not UTF-8`);let d=new ot(e,c,n,t);d.seed(0,o),d.fetches+=1,d.bytesFetched+=o.length;let h=new rt(d,l),u=new Map;for await(let{values:m}of h.tableScan(1)){let[w,x,S,g,b]=m;typeof w=="string"&&typeof x=="string"&&typeof S=="string"&&typeof g=="number"&&u.set(x,{type:w,name:x,tableName:S,rootPage:g,sql:typeof b=="string"?b:""})}return new r(d,h,u)}rootPage(e){let t=this.objects.get(e);if(!t)throw new Error(`SQLite database has no object named ${e}`);return t.rootPage}indexOn(e){let t=[...this.objects.values()].find(n=>n.type==="index"&&n.tableName===e);if(!t)throw new Error(`SQLite table ${e} has no index`);return t.rootPage}byRowid(e,t){return this.btree.tableRowid(this.rootPage(e),t)}prefetchRows(e,t,n){return this.btree.prefetchRowidRange(this.rootPage(e),t,n)}scan(e){return this.btree.tableScan(this.rootPage(e))}indexSeekLE(e,t){return this.btree.indexSeekLE(this.indexOn(e),t)}indexScanFrom(e,t){return this.btree.indexScanFrom(this.indexOn(e),t)}has(e){return this.objects.has(e)}};var Xt="GBZ-base version 4",st=class extends Error{name="ForwardOnlyIndexError";constructor(){super("the haplotype index was written with --forward-only, which cannot name the walks stored against their reference (about half of them); rebuild it with gbz-haplotype-index without --forward-only")}},it=class extends Error{name="SchemaVersionError";found;constructor(e){super(e===void 0?"not a gbz-base database: its Tags table has no version":`unsupported database schema "${e}"; this reader understands "${Xt}"`),this.found=e}},at=class{sequenceLen;handle;edges;bwt;encodedSequence;next;decoded;constructor(e,t,n,o,s){this.handle=e,this.edges=t,this.bwt=n,this.encodedSequence=o,this.next=s,this.sequenceLen=Dn(o)}get id(){return A(this.handle)}get orientation(){return ge(this.handle)}get sequence(){return this.decoded??=zn(this.encodedSequence),this.decoded}successors(){return this.edges.filter(e=>e.node!==0).map(e=>e.node)}gbwt(){if(this.edges.length===0)throw new Error(`GBWT record for handle ${this.handle} is empty`);return new ze(this.edges,this.bwt)}};function T(r,e){if(typeof r!="number")throw new Error(`${e} is not a number in the database`);return r}function ft(r,e){if(typeof r!="string")throw new Error(`${e} is not text in the database`);return r}function Kt(r,e){if(!(r instanceof 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of["Tags","HaplotypeSamples","HaplotypeLengths"])i.rootPage(h);a.indexTags=await xr(i);let c=a.indexTags.get("haplotype_index_paths"),l=await a.tag("paths");if(c!==l)throw new Error(`haplotype index was built for ${c??"an unknown number of"} paths but the graph has ${l}`);let p=a.indexTags.get("haplotype_index_nodes"),d=await a.tag("nodes");if(p!==void 0&&p!==d)throw new Error(`haplotype index was built for a graph with ${p} nodes but this one has ${d}`);if(a.indexTags.get("haplotype_index_orientations")==="forward")throw new st}return a}tags(){return this.tagCache??=xr(this.sqlite),this.tagCache}async tag(e){return(await this.tags()).get(e)}prefetchRecords(e,t){return this.sqlite.prefetchRows("Nodes",e,t)}async getRecord(e){let t=await this.sqlite.byRowid("Nodes",e);if(!t)return;let n=t[4];return new at(e,Bn(Kt(t[1],"Nodes.edges")),Kt(t[2],"Nodes.bwt"),Kt(t[3],"Nodes.sequence"),typeof n=="number"?n:void 0)}paths(){return this.pathCache??=(async()=>{let e=[];for 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t||(t=this.walkPathLength(e),this.pathLengths.set(e,t),t.catch(()=>this.pathLengths.delete(e))),t}async walkPathLength(e){let t=this.hasHaplotypeIndex?await this.haplotypeLength(e):void 0;if(t===void 0){let n=await this.indexedPosition(e,Number.MAX_SAFE_INTEGER);if(!n){let i=await this.getPath(e);throw new Error(`Path ${i?$(i.name,i.name.fragment):e} has not been indexed for random access`)}let o=n.pathOffset,s=n.pos;for(;;){let i=await this.getRecord(s.node);if(!i)throw new Error(`Node ${s.node} does not exist in the graph`);o+=i.sequenceLen;let a=i.gbwt().lf(s.offset);if(!a||a.node===0)return o;s=a}}return t}async pathFragmentsForRange(e,t,n){if(n<=t)return[];let o=await this.pathsNamed(e),s=o.filter(f=>f.name.fragment<=t).slice(-1),i=o.filter(f=>f.name.fragment>t&&f.name.fragment<n);return(await Promise.all([...s,...i].map(async f=>({path:f,start:f.name.fragment,end:f.name.fragment+await this.pathLength(f.handle)})))).filter(f=>t<f.end)}async subgraphForFragment(e,t,n,o){let{keep:s,...i}=o;if(s!==void 0&&!this.hasHaplotypeIndex)throw new Error("keep needs the haplotype index: this database cannot name its walks");let{sample:a,contig:f,haplotype:c}=e.path.name,l={sample:a,contig:f,haplotype:c},p=Math.max(t,e.start),d=Math.min(n,e.end),h=o.haplotypes??"all",u=h==="all"||h==="distinct",m;return s!==void 0&&h==="all"?m=await ur(this,l,p,d,{...i,keep:s}):(m=await Je(this,l,p,d,i),this.hasHaplotypeIndex&&u&&(await m.identifyPaths(),s!==void 0&&m.keepHaplotypes(s))),m}async getSubgraphForRange(e,t,n,o={}){let[s]=await this.pathFragmentsForRange(e,t,n);return s?this.subgraphForFragment(s,t,n,o):void 0}async getAlignmentsForRange(e,t,n,o={}){let s=[];for(let i of await this.pathFragmentsForRange(e,t,n)){let a=await this.subgraphForFragment(i,t,n,o);s.push(...a.alignments())}return s}async graphName(){let e=new Map;for(let[n,o]of await this.tags())n.startsWith("gbz_")&&e.set(n.slice(4),o);let t={name:void 0,subgraph:new Map,translation:new Map};try{t=Qn(e)}catch{}return t}async hasChainLinks(){let e=await this.tag("chain_links");return e!==void 0&&Number(e)>0}get hasHaplotypeIndex(){return this.index!==void 0}get companion(){if(!this.index)throw new Error("no haplotype index was opened with this database");return this.index}async haplotypeSampleInterval(){let e=this.indexTags.get("haplotype_index_interval");return e===void 0?void 0:Number(e)}async haplotypeAnchorSpacing(){let e=this.index?.has("HaplotypeAnchors")?this.indexTags.get("haplotype_index_anchor_spacing"):void 0;return e===void 0?void 0:Number(e)}async haplotypeAnchor(e,t){let n=await this.companion.indexSeekLE("HaplotypeAnchors",[e,t]),o=n?.[0]===e&&n[1]===t?await this.companion.byRowid("HaplotypeAnchors",T(n[2],"HaplotypeAnchors rowid")):void 0;return o?{node:T(o[2],"HaplotypeAnchors.node_handle"),pathOffset:T(o[3],"HaplotypeAnchors.path_offset")}:void 0}haplotypeSamplesAtNode(e){return this.haplotypeSamplesInRange(e,e)}sampleFromRow(e){return{node:T(e[0],"HaplotypeSamples.node_handle"),offset:T(e[1],"HaplotypeSamples.node_offset"),pathHandle:T(e[2],"HaplotypeSamples.path_handle"),orientation:T(e[3],"HaplotypeSamples.orientation")===0?"forward":"reverse",pathOffset:T(e[4],"HaplotypeSamples.path_offset")}}async haplotypeSamplesInRange(e,t){let n=[];for await(let o of this.companion.indexScanFrom("HaplotypeSamples",[e,0])){if(T(o[0],"HaplotypeSamples.node_handle")>t)break;let i=await this.companion.byRowid("HaplotypeSamples",T(o[2],"HaplotypeSamples rowid"));i&&n.push(this.sampleFromRow(i))}return n}async haplotypeSampleAt(e,t){let n=await this.companion.indexSeekLE("HaplotypeSamples",[e,t]);if(n?.[0]!==e||n[1]!==t)return;let o=await this.companion.byRowid("HaplotypeSamples",T(n[2],"HaplotypeSamples rowid"));return o?this.sampleFromRow(o):void 0}async haplotypeLength(e){let t=await this.companion.byRowid("HaplotypeLengths",e);return t?T(t[1],"HaplotypeLengths.length"):void 0}async indexedRow(e){let t=await this.sqlite.byRowid("ReferenceIndex",e);if(!t)throw new Error("ReferenceIndex row referenced by its index is missing");return{pathOffset:T(t[1],"ReferenceIndex.path_offset"),pos:{node:T(t[2],"ReferenceIndex.node_handle"),offset:T(t[3],"ReferenceIndex.node_offset")}}}async indexedRowid(e,t){let n=await this.sqlite.indexSeekLE("ReferenceIndex",[e,t]);return n?.[0]===e?T(n[2],"ReferenceIndex rowid"):void 0}async indexedPosition(e,t){let n=await this.indexedRowid(e,t);return n===void 0?void 0:this.indexedRow(n)}async indexedPositionsBetween(e,t,n){let[o,s]=await Promise.all([this.indexedRowid(e,t),this.indexedRowid(e,n)]),i=[];if(o!==void 0&&s!==void 0){await this.sqlite.prefetchRows("ReferenceIndex",o,s+1);for(let a=o;a<=s;a++)i.push(await this.indexedRow(a))}return i}};var ct=class extends Error{constructor(t,n){super(n.length===0?`the graph names no reference sample (gbwt_reference_samples) and the anchor "${t}" maps to none; set referenceSample`:`the anchor "${t}" is none of the graph's reference samples (${n.join(", ")}); set referenceSample or map it through assemblyNameToPanSN`);this.name="NoReferenceSampleError"}},lt=class extends Error{constructor(t,n,o){super(`this ${n.toLocaleString()} bp window reads more than nodeLimit (${t.toLocaleString()}) graph nodes; zoom in to about ${o.toLocaleString()} bp or raise nodeLimit`);this.name="NodeLimitError"}};function J(r){return`${r.sample}#${r.haplotype}`}function br(r,e){let t=J(r);return e===void 0||e.some(n=>ue(t,n))}async function Sr(r){return(await r.tag("gbwt_reference_samples")??"").split(/\s+/).filter(e=>e!=="")}function ls(r,e){let t=r.toLowerCase(),n=_n(r)?.toLowerCase();return e.find(o=>o===r)??e.find(o=>o.toLowerCase()===t)??e.find(o=>o.toLowerCase()===n)}function Zt({configured:r,anchorPrefix:e,referenceSamples:t}){if(r!=="")return r;let n=ls(Pn(e),t)??(t.length===1?t[0]:void 0);if(n===void 0)throw new ct(e,t);return n}async 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without a targetAssemblyName`);this.name="PairTargetError"}},An=class extends Error{constructor(t,n){super(`the graph is cut on its reference, ${n}; a window on ${t} has no reference coordinates to cut at. Open the graph from a ${n} view, and find this haplotype's lane there`);this.name="HaplotypeWindowError"}};function So(r,e){let t=J(e);return r[t]??r[e.sample]??t}function Ks(r,e){return`${J(r)}#${r.contig}@${e.start.node}.${e.start.offset}`}function Xs({alignment:r,assemblyName:e,refName:t,lane:n}){let{refStart:o,refEnd:s,strand:i,cigar:a}=r;if(!(!r.resolved||s<=o)){let{name:f,hapStart:c,hapEnd:l}=r,p=Ks(f,r),d={uniqueId:p,assemblyName:e,refName:t,start:o,end:s,type:"match",strand:i==="-"?-1:1,CIGAR:a,syntenyId:p,mate:{refName:f.contig,start:c,end:l,assemblyName:n}};return new se(d)}}function Zs({pair:r,lane:e,mateLane:t}){let n=`${J(r.target)}#${r.target.contig}:${r.targetStart}-${r.targetEnd}|${J(r.query)}#${r.query.contig}:${r.queryStart}-${r.queryEnd}`;return new se({uniqueId:n,assemblyName:e,refName:r.target.contig,start:r.targetStart,end:r.targetEnd,type:"match",strand:r.strand==="-"?-1:1,CIGAR:r.cigar,syntenyId:n,identity:r.matches/Math.max(r.columns,1),numMatches:r.matches,blockLen:r.columns,mate:{refName:r.query.contig,start:r.queryStart,end:r.queryEnd,assemblyName:t}})}var xn=r=>!("uri"in r)||r.uri!=="",En=class extends qt{constructor(){super(...arguments);this.graph=(0,bn.cachedSetup)({label:"Opening pangenome database",setup:async()=>{let t=this.getConf("gbzDbLocation"),n=this.getConf("haplotypeIndexLocation"),o=xn(n)?n:await Cr(t,this.pluginManager),s=await Oe.open((0,Ae.openLocation)(t,this.pluginManager),o?{haplotypeIndex:(0,Ae.openLocation)(o,this.pluginManager)}:{}),i=this.getConf("assemblyNames")[0];if(i===void 0)throw new Error("GbzBaseSyntenyAdapter needs assemblyNames: its first entry is the assembly the reference sample is loaded as");let a=await Sr(s),f=Zt({configured:this.getConf("referenceSample"),anchorPrefix:me(this,i),referenceSamples:a});return{db:s,anchor:i,referenceSample:f,referenceSamples:a}}});this.gaf=(0,bn.cachedSetup)({label:"Opening reads",setup:async()=>{let t=this.getConf("readsLocation"),n=this.getConf(["readsIndex","location"]),o=this.pluginManager;if(!xn(t))return;let s=(0,Ae.openLocation)(t,o);return new pt(s,xn(n)?new Rn({filehandle:s,...(0,Ae.openTabixIndexFilehandle)(n,this.getConf(["readsIndex","indexType"]),o)}):void 0)}})}async referenceQuery(t,n){let{db:o,referenceSample:s}=await this.graph(n);return vr(o,s,t)}async getHaplotypes(t={}){let{db:n,referenceSamples:o}=await this.graph(t),s=new Map;for(let i of await n.paths()){let a=J(i.name),f=s.get(a);f?f.contigs.includes(i.name.contig)||f.contigs.push(i.name.contig):s.set(a,{prefix:a,sample:i.name.sample,haplotype:i.name.haplotype,contigs:[i.name.contig],isReference:o.includes(i.name.sample)})}return[...s.values()]}async getHeader(t={}){let{anchor:n,referenceSample:o,referenceSamples:s}=await this.graph(t),i=$t(this),a=[];for(let f of await this.getHaplotypes(t))f.sample!==o&&a.push({name:So(i,f),label:f.prefix,group:f.sample});return{hasCoarseTier:!1,anchorAssemblyName:n,referenceSample:o,referenceSamples:s,lanes:a}}async getRefNames(t={}){let{db:n,anchor:o,referenceSample:s}=await this.graph(t),{assemblyName:i}=t,a=i===o?void 0:me(this,i),f=(await n.paths()).filter(c=>i===o?c.isIndexed&&c.name.sample===s:ue(J(c.name),a)).map(c=>c.name.contig);return[...new Set(f)]}keepPredicate(t,n){let o=t===void 0||t.length===0?void 0:t.map(s=>me(this,s));return o===void 0&&n===void 0?void 0:s=>br(s,o)&&(n===void 0||ue(J(s),n))}async getSubgraph(t,n={}){let{db:o,anchor:s}=await this.graph(),{assemblyName:i,refName:a,start:f,end:c}=t;if(i!==s)throw new An(i,s);let l=await this.referenceQuery(a,{}),p=this.keepPredicate(n.haplotypes);return Ir(o,l,f,c,{context:this.getConf("context"),snarls:this.getConf("subgraphSnarls"),limit:this.getConf("nodeLimit"),signal:n.signal,...p===void 0?{}:{keep:p}})}async getReads(t,n={}){let o=await this.gaf(n);return o?o.readsOver(new Set(t),n):{records:[],total:0}}async laneHaplotypes(t,n){let o=me(this,t);return(await this.getHaplotypes(n)).filter(s=>ue(s.prefix,o))}async referencePieces(t,n,o,s){let{db:i,referenceSample:a}=await this.graph(s),f=(await i.paths()).filter(l=>l.isIndexed&&l.name.sample===a&&l.name.contig===t&&l.name.fragment>n&&l.name.fragment<o).map(l=>l.name.fragment),c=[n,...[...new Set(f)].sort((l,p)=>l-p),o];return c.slice(1).map((l,p)=>({start:c[p],end:l}))}async anchorFeatures(t,n){let{db:o}=await this.graph(n),{assemblyName:s,refName:i,start:a,end:f}=t,c=me(this,n.targetAssemblyName),l=$t(this),p=this.keepPredicate(n.haplotypes,c),d=await this.referenceQuery(i,n),h=this.getConf("nodeLimit");return(d?await(0,Sn.updateStatus)(`Reading graph ${i}:${a.toLocaleString()}-${f.toLocaleString()}`,n.statusCallback,()=>o.getAlignmentsForRange(d,a,f,{context:this.getConf("context"),haplotypes:"all",limit:h,signal:n.signal,...p===void 0?{}:{keep:p}}).catch(m=>{throw Te(m,h,f-a)??m})):[]).flatMap(m=>{let w=m.resolved?Xs({alignment:m,assemblyName:s,refName:i,lane:So(l,m.name)}):void 0;return w===void 0?[]:[w]})}async pairFeatures(t,n,o){let{targetAssemblyName:s}=o;if(s===void 0)throw new In(n);let{db:i}=await this.graph(o),{refName:a,start:f,end:c}=t,l=await this.laneHaplotypes(n,o),p=await this.laneHaplotypes(s,o),d=[...l,...p],h=await this.referenceQuery(a,o),u=this.getConf("nodeLimit"),m=await i.haplotypeAnchorSpacing()!==void 0,w=(g,b)=>i.getSubgraphForRange(g,b.start,b.end,{context:this.getConf("context"),haplotypes:"all",limit:u,signal:o.signal,keep:y=>d.some(v=>v.sample===y.sample&&v.haplotype===y.haplotype)}).catch(y=>{throw Te(y,u,c-f)??y}),x=h&&m&&l.length>0&&p.length>0?(await(0,Sn.updateStatus)(`Reading ${n} against ${s}`,o.statusCallback,async()=>Promise.all((await this.referencePieces(a,f,c,o)).map(g=>w(h,g))))).filter(g=>g!==void 0):[];return x.every(g=>{let b=g.stats.anchorWalk;return b!==void 0&&b.fallback===void 0})?x.flatMap(g=>l.flatMap(b=>p.flatMap(y=>g.pairAlignments({target:b,query:y,bases:!1}).map(v=>Zs({pair:v,lane:n,mateLane:s}))))):[]}getFeatures(t,n={}){return(0,vo.ObservableCreate)(async o=>{let{db:s,anchor:i}=await this.graph(n);if(!s.hasHaplotypeIndex)throw new vn;if(t.assemblyName===i){let a=n.queryAssemblyName===void 0?await this.anchorFeatures(t,n):await this.pairFeatures(t,n.queryAssemblyName,n);for(let f of a)o.next(f)}o.complete()},n.signal)}};export{An as HaplotypeWindowError,vn as NoHaplotypeIndexError,ct as NoReferenceSampleError,lt as NodeLimitError,In as PairTargetError,En as default,Xs as fragmentFeature,J as haplotypePrefix,So as laneAssemblyName,Te as nodeLimitError,Zs as pairFeature,Zt as resolveReferenceSample};
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